Scientists in hunt for new schizophrenia treatment

A UBC neuroscientist has received a $300,000 grant to take a new look at how
schizophrenia is affected by dopamine, the natural chemical that regulates brain
activity.

Charles Yang, an assistant professor in the Dept. of Psychology, is one of
only six researchers in North America to receive a grant from the Montreal-based
EJLB Foundation to investigate schizophrenia, the devastating mental illness
that strikes one out of every 100 Canadians.

Yang's study will focus on the functions of the brain's prefrontal cortex.
Schizophrenia symptoms, including delusions, hallucinations and disorganized
thoughts and behaviour, often arise from the dysregulated interplay between
the prefrontal cortex and other regions of the brain.

Yang's work could lead to the development of a new generation of anti-psychotic
drugs which target prefrontal cortex cells.

"Think of the prefrontal cortex as the human equivalent of a computer's central
processing unit," Yang said. "Aided by dopamine, it plays a key role in communicating
with other regions of the brain and organizing short-term memory in a sequential
manner that allows us to perform our daily activities. This process is defective
in schizophrenia."

Many researchers have debated whether it is too much or too little dopamine
that brings on schizophrenia symptoms. Yang has framed the problem a different
way. He believes it is a dysregulation of brain dopamine levels, swinging back
and forth from high to low, that results in the diverse symptoms.

To test his theory, Yang and his collaborators, who include Dr. Susan Sesack
of the University of Pittsburgh, are conducting experiments that use innovative
electrophysiological and neuroanatomical techniques to measure the exact changes
in electrical signals within the brain.

For example, Yang will be taking his measurements from the dendrites -- fine,
branch-like fibres radiating from the brain cells, or neurons. Dendrites act
like antennas to receive signals from other parts of the brain, passing the
information along to the neurons with the help of dopamine.

Until now, such measurements were done only in the main body of the neuron,
which Yang compares to listening to a conversation two rooms away: you can hear
that something is being said, but the words are not clear.

Yang's laboratory will also use new techniques to examine the roles of GABA
interneurons, which release inhibitory transmitters that work with dopamine
to perform a fine-tuning function in the prefrontal cortex.

Yang proposes two scenarios for schizophrenia.

In the first, a low dopamine level parallels a reduction of the function of
GABA interneurons, so the dendrites receive an unregulated blast of signals
from other parts of the brain, resulting in thought disorders.

In the second scenario, perhaps found most often in younger schizophrenics,
an excess of dopamine enhances the inhibitory action of the GABA interneurons,
strangling signals in the dendrites.

As incoming signals from other parts of the brain are reduced, the high levels
of dopamine may create reverberating signals within the prefrontal cortex. This
may explain the aimless, repetitive actions sometimes demonstrated by schizophrenics.